The majority of human mammary tumors that contain significant amounts of estrogen receptor, and about one-third of all endometrial carcinomas, respond to some form of endocrine therapy. Yet the mechanism by which hormones control cell growth in either normal or tumor cells is not known. We therefore propose an investigation into this problem at the fundamental level of gene activation in the female reproductive track. Our goal will be to create a library of mRNAs (a cDNA library) that are induced by estradiol in the endometrial cells of rat uterus. In addition to the shotgun approach in which random responsive mRNAs will be cloned, we will attempt to enrich a preparation of RNA for messages that code specifically for the 64K protein that we find to be secreted by endometrial cells in response to estradiol. These cDNAs will then be used to probe the kinetics of induction and deinduction of the various mRNAs that respond to estradiol and antiestrogen treatment and to progesterone administration. We will examine their fluctuation during the normal estrus cycle and during early uterine development. In addition, we will determine whether any of these cDNA probes cross-react with mRNAs that are found in a cell line derived from a human endometrial carcinoma (HEC-59). Finally, we will attempt to identify the chromosomal DNA sequences from which these mRNAs are transcribed. A rat genomic library will be probed with our cDNAs in order to find hybrid phages containing homologous genomic inserts. These inserts will be mapped and partially sequenced with the goal of identifying possible regulatory regions that may be responsible for the hormonal control seen in this set of genes.